1. Field of the Invention
The invention relates to novel compositions for use in effecting therapeutic percutaneous embolization, and more particularly, to compositions for the embolization of blood vessels. The invention also relates to embolization methods using the above compositions.
2. Prior Art
Therapeutic percutaneous embolization has been proven to be an effective tool in managing various disorders such as vascular lesions, aneurysms, and arteriovenous malformations. This technique is also very effective in treating tumors by the careful and selective obliteration of the arterial supply of neoplasms where such blood vessels enter the tumor and bring it the nutrients which it requires. Percutaneous embolization has also been known to be a lifesaving procedure in certain cases of arteriovenous malformations.
Several methods have heretofore been proposed for performing percutaneous embolization. Thus, a balloon embolization technique was developed according to which a catheter with a balloon at its end was used (W. Taki et al, Surg. Neurol. 12, p.p. 363-365, 1979; G. Deburn et al, J. Neurosurg., 1978, p.p. 635-649). According to this technique, the catheter must be flexible enough to be introduced into arteries of complex configuration. The inflatable balloon is attached to the catheter through a specially designed joint which is twisted off when the inflated balloon is in the target area, i.e., the vascular lesion which is the aim of the treatment. The released balloon then seals off the blood vessel itself. The disadvantage of this method is that the sealing lasts only for a few days because the balloon eventually deflates.
Another method for embolization was proposed according to which a liquid containing a readily polymerizable monomer and a catalyst for the polymerization is introduced through the catheter into the balloon. It was suggested to use 2-hydroxyethyl methacrylate (HEMA) as the monomer. (W. Taki, et al, Surg. Neurol. 13, p.p. 140-142 (1980)). The disadvantages associated with this method are the difficulty in monitoring the proper volume of liquid supplied to the balloon so as to have an adequate embolization occur; and the possibility of polymerization occurring in the catheter (as opposed to the blood vessel) which would result in failure of the entire procedure.
Another quite efficient embolization method was suggested, according to which radioopaque Silastic.RTM. spheres are used to occlude blood vessels. (S. K. Hilal et al, J. of Neurosurg. 43, p.o. 275-287 (1975)). Depending upon the precise nature of the case, and the blood vessel characteristics, the number of spheres required ranged from 30 to 250 and varied from 1 mm to 2.5 mm in diameter. The spheres are delivered through a catheter by a special device and at all times are immersed in a sterile physiological solution. Though providing adequate and long lasting embolization, this system has several drawbacks. A large amount of fluid is required for injection which can be a limiting factor in some cases and, in addition, the embolization procedure is long and only one or two vessels can be occluded in any one day.
Cross-linked gels of hyaluronan (also and formerly known as hyaluronic acid) are known, and their preparation is described in U.S. Pat. Nos. 4,582,865; 4,605,691 and 4,636,524. In addition, the slightly modified hyaluronan known as hylan is described in published U.K. application No. 2,172,295A.